The interaction between finasteride and corticosterone levels: implications for depression-, and anxiety-like
Jose Nayana1, Byrathnahalli S Shankaranarayana Rao1, Bettadapura N Srikumar2
1Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Hosur Road, Bengaluru, 560029, India.
Rationale:
Finasteride is FDA-approved for the treatment of hair loss and in older men for benign prostatic hyperplasia. However, some patients treated with finasteride reported suicidal ideation, depression, and anxiety. The neurobiological mechanisms underlying this are not clearly understood. Previously, we showed that short-term finasteride administration results in depression- and anxiety-like behaviour. Since finasteride treatment is long-term in the clinic, we examine the effects of chronic finasteride administration in the current study.
Objective:
This study aims to understand the behavioral, cellular, and molecular changes in male rats following 21 days of finasteride (3 mg, 10 mg, and 30 mg/Kg) administration.
Methods:
Depression-like behavior was evaluated using forced swim (FST), sucrose preference (SPT), and splash tests. Anxiety-like behavior was assessed using elevated plus maze (EPM), open field (OFT), light-dark (LDT), Vogel's conflict (VCT), and home cage emergence (HCET), and depression-related anxiety in novelty-suppressed feeding task (NSFT) tests. Hippocampal synaptic plasticity was assessed by field excitatory post-synaptic potentials (fEPSP) recordings in the Schaffer-collateral-CA1 synapses, and plasma corticosterone levels were estimated using ELISA.
Results:
Chronic finasteride administration induced depression-like and anxiety-like behavior in SPT and EPM, respectively, but not in the other paradigms. There was a modest decrease in long-term potentiation in the hippocampus. Interestingly, there was an increase in the plasma corticosterone levels with 6 days of finasteride administration, but not after 14 or 21 days of administration.
Conclusions:
Chronic administration of finasteride did not induce a robust depression- and anxiety-like behavior and modestly affected synaptic plasticity. This could be potentially because of the adaptive response observed in the plasma corticosterone levels.
Insights
Chronic finasteride administration in rats did not cause significant depression or anxiety behaviors. However, it showed a modest impact on hippocampal synaptic plasticity, possibly due to adaptive corticosterone level changes.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Finasteride, approved for hair loss and benign prostatic hyperplasia, has been linked to mood disturbances like depression and anxiety.
- Previous studies indicated short-term finasteride use causes depression- and anxiety-like behaviors.
- The neurobiological underpinnings of these adverse effects remain unclear, necessitating investigation into chronic administration.
Purpose of the Study:
- To investigate the behavioral, cellular, and molecular effects of chronic finasteride administration in male rats.
- To assess depression- and anxiety-like behaviors following prolonged finasteride exposure.
- To evaluate impacts on hippocampal synaptic plasticity and corticosterone levels.
Main Methods:
- Male rats received chronic finasteride (3, 10, or 30 mg/Kg) for 21 days.
- Behavioral tests included forced swim, sucrose preference, splash, elevated plus maze, open field, light-dark, Vogel's conflict, home cage emergence, and novelty-suppressed feeding.
- Hippocampal synaptic plasticity was measured via fEPSP, and plasma corticosterone levels were determined by ELISA.
Main Results:
- Chronic finasteride induced depression-like behavior in the sucrose preference test and anxiety-like behavior in the elevated plus maze.
- A modest decrease in hippocampal long-term potentiation was observed.
- Plasma corticosterone levels increased after 6 days but normalized by days 14 and 21.
Conclusions:
- Chronic finasteride administration did not produce robust depression- and anxiety-like behaviors in rats.
- Synaptic plasticity was only modestly affected, suggesting potential adaptation.
- Adaptive changes in plasma corticosterone levels may mitigate behavioral and cellular effects over time.
